Cadaveric liver transplantation is recognized as the optimal therapy for end stage liver disease, with marked improvement in results over the last two decades. With the increasing success of this treatment, the demand for suitable donor organs has also risen, resulting in a large discrepancy between the number of transplantable organs and the number of patients waiting. This imbalance has led to the development of living donor liver transplantation (LDLT) as an additional method to increase organ supply. The exact indications for this procedure as well as long-term results and potential impact on the healthy donor are questions that remain unanswered. These issues form the basis for this research protocol, which proposes a longitudinal cohort study of live donor liver transplant recipients and their donors across eight transplant centers with an extended period of follow-up. The aims of this cohort study will be the formation of a core database containing information collected pre-transplant, intraoperatively and post-transplant. At least 250 living liver donor/recipient pairs and an equal or greater number of cadaveric recipients will be followed for a minimum of two years to provide critically needed information on the safety and efficacy of living donor liver transplantation, the potential impact on disease progression and recurrence, and ultimately to better define the specific role of living donor liver transplantation in the management of end stage liver disease.In addition to core data collection, this cohort study will offer an opportunity to address specific research questions unique to the setting of LDLT. The first project focuses on patients with hepatitis C, the most common indication for transplantation in the U.S. The kinetics of recurrent hepatitis C viral load post-transplantation will be compared in living donor and matched cadaveric recipients, and the effect of pre-transplant interferon treatment on the tempo and severity of recurrence evaluated. The second project focuses on optimization of pain control in living donors, comparing the use of preemptive thoracic epidural catheter analgesia delivery with patient controlled intravenous analgesia, and using pain scores and quality of life instruments to evaluate the impact of these treatments on long and short-term outcomes.We anticipate that the study will provide the necessary information to aid physicians in the counseling of patients regarding transplant options, and help prospective donors and recipients to better understand the risks and benefits of the procedure. Additionally, the information gained through this cohort study can be expected to impact the entire living donor transplantation procedure itself, by identifying factors that can be modified pre-transplantation, intraoperativiely, and post-transplantation to improve donor and recipient outcomes.